On March 8, 2010, Health Canada released its final guidance documents relating to the approval pathway for subsequent entry biologics (SEBs) in Canada. Notably, the pathway is not set in regulation, but rather, in guidance document. Such documents, Health Canada's SEB guidance document acknowledges, are administrative instruments not having force of law. Alternate approaches to the principles and practices described in guidance documents may be acceptable provided they are supported by adequate justification.

Consultations had been ongoing since January 2008, with the release of the first draft guidance for SEB sponsors. A further draft was released in March 2009, and in addition, at the same time, draft amendments were released relating to two other guidance documents, the Patented Medicines (Notice of Compliance) Regulations and the Food and Drug Regulations, as they relate to data protection/data exclusivity.

The final SEB guidance contains a few differences from the March 2009 draft guidance. The most controversial element of the pathway includes the ability for an SEB sponsor to use a foreign reference product on which to base its comparability studies, for the purpose of demonstrating similarity. A foreign version of a reference product can be used even where the Canadian version has not been marketed (although there is a requirement that the Canadian version has been approved by Health Canada). The final guidance clarifies that an SEB sponsor must name the Canadian-approved product and must provide evidence that the foreign reference product is a suitable proxy for the Canadian product. The submission must confirm that the foreign product is marketed by the same innovator company or corporate entity that is approved to market the medicinal ingredient in the same dosage form in Canada.

The guidance documents on Data Protection and the NOC Regulations have been revised to reflect Health Canada's application of these regulations to SEBs, and the obligations on SEB manufacturers to respect these rules. Specifically, the guidance documents provide that, where the SEB pathway for approval is followed, the SEB manufacturer will be required to observe the requirements of both sets of regulations. This is true whether the reference product is Canadian or a foreign version of a Canadian product. In either case, pursuing the SEB pathway will amount to a comparison that triggers the application of both sets of regulations, to the extent they are applicable.

The SEB guidance contains a new element, in explicitly stating that in the event that the trials suggest superiority of the SEB over the reference biologic drug, superiority observed will be assessed for clinical relevance including its impact on safety. In the event that the superiority observed is considered clinically meaningful and/or is associated with increased adverse drug reactions, the product will not be considered an SEB.

Other changes include a specific requirement that the SEB product monograph state that the product is an SEB. In particular, the guidance provides that in the product monograph, a statement will follow the description of the SEB to indicate that similarity between the SEB and the reference product was established in accordance with the Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biologics (SEBs).

The final SEB guidance does not address interchangeability of SEBs for their innovative counterparts, other than to say that "Authorization of an SEB is not a declaration of pharmaceutical or therapeutic equivalence to the reference biologic drug".

The Guidance for Sponsors, Information and Submission Requirements for Subsequent Entry Biologics (SEBs), may be found at: http://www.hc-sc.gc.ca/dhp-mps/brgtherap/applic-demande/guides/seb-pbu/seb-pbu_2010-eng.php

The updated Guidance Document: Patented Medicines (Notice of Compliance) Regulations may be found at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/patmedbrev/pmreg3_mbreg3-eng.php

The updated Guidance Document: Data Protection under C.08.004.1 of the Food and Drug Regulations may be found at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/data_donnees_protection-eng.php